POS1303 METHOTREXATE RESPONSE IN PEDIATRIC NON-INFECTIOUS UVEITIS
Authors: S. Angeles-Han, A. Cassedy, T. Hennard, M. Altaye, H. Brunner, E. Dosunmu, A. Grom, M. Henrickson, J. Huggins, S. Lopper, D. J. Lovell, R. Sisk, T. Ting, A. Kaufman, V. Utz
Journal: Annals of the Rheumatic Diseases (2022)

Background Children with chronic non-infectious uveitis (NIU) are at risk for sight-threatening complications. Methotrexate (MTX) is the preferred first-line systemic treatment. Initial therapeutic response takes 3-6 months to achieve NIU control, leading to prolonged glucocorticoid use. Moreover, at least 50-70% of children fail to fully respond and may accrue ocular damage while awaiting MTX response. Objectives To identify features of children with NIU that are associated with MTX failure. Methods We included children who started MTX monotherapy for NIU. We collected demographics, NIU features (type, location, &amp; complications), ANA status, and clinical examination. We characterized children as MTX responders or non-responders. MTX responders are those whose NIU was controlled, defined by: 1) inactive graded by SUN criteria, 2) absence of new or worsening complications, and 3) requirement for ≤2 drops of prednisolone acetate and no oral glucocorticoids. Results Of 47 NIU children, 68% were MTX non-responders (Table 1), having a longer duration of NIU (Odds Ratio [OR]=1.28, [CI=1.03-1.8], p =0.023) and developing more ocular complications (OR=1.95 [CI=1.23-3.38], p=0.017), (ROC Area Under the Curve = 0.85). MTX non-responders were more likely to have anterior and/or posterior synechiae (p = 0.001), cataracts (p=0.015), and ocular hypertension (p=0.039). Treatment included adalimumab: 27, infliximab: 14, tocilizumab: 5, golimumab: 4, etanercept: 3, and abatacept: 2. Table 1. Comparison of children with NIU based on MTX response. Responders n=15 Non-responders n=32 Caucasian 14 (93) 27 (84) Hispanic or Latino 0 (0) 3 (9) Female 12 (80) 23 (72) Age of NIU onset, yrs, median (IQR ) 4.3 (2.9 – 12.3) 4.6 (2.8 - 7.0) Duration of NIU, yrs, median, (IQR ) 4.1 (2.6 – 5.3) 8.2 (4.7 - 11.3) JIA-NIU 10 (67) 25 (78) Idiopathic CAU 2 (13) 3 (9) Other 3 (20) 4 (12) Bilateral disease 12 (80) 23 (72) Anterior 12 (86) 29 (91) Presenting BCVA (LogMAR) worst eye, median (IQR ) 0.2 (0.1 – 0.3) 0.1 (0.0 - 0.2) Average # of total complications/person, median (IQR ) 1 (0 – 2) 2.5 (1.0 – 5.5) ANA positive 10 (67) 26 (81) Earliest ESR 8 (6– 18) 12 (8 - 18) Earliest Vitamin D 32 (26 – 35) 31 (23 - 35) Time on MTX, months, median (IQR ) 35 (19 - 64) 19 (7 - 74) Time from systemic or NIU onset to MTX, yrs, median (IQR ) 0.3 (0.1 – 0.5) 0.2 (0.0 - 0.8) MTX PO 6 (40) 19 (59) MTX SC 13 (87) 31 (97) We performed a sub analysis of children with idiopathic chronic anterior NIU (CAU) and JIA-associated NIU that included children who failed MTX due to intolerance/toxicity (Figure 1). Using Cox proportional hazard regression, 8 idiopathic CAU failed MTX earlier than 38 JIA-associated NIU (HR 2.77, [CI-=1.06-7.27], p=0.039). Results were similar with the inclusion of other types of NIU (p=0.088) (e.g., HLA-B27, non-anterior idiopathic or with systemic disease). Figure 1. Kaplan-Meier curve showing freedom from TNFi (mos) stratified by diagnosis Conclusion Two out of three children with NIU fail initial MTX monotherapy, exposing them to increased accrual of ocular complications prior to biologic starts. The risk for delay in starting tumor necrosis factor α inhibitors (TNFi) seems higher with CAU. Future studies will examine risk factors that predict MTX response in NIU. References [1]McCracken C, Angeles-Han ST, et.al. Timing of infliximab and adalimumab initiation despite methotrexate in children with chronic non-infectious anterior uveitis. Eye (Lond). 2019;33(4):629-39. [2]Henderson LA, Angeles-Han ST, et.al., Medication use in juvenile uveitis patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry. Pediatr Rheumatol Online J. 2016;14(1):9. [3]Cooper A, et.al., Failure of methotrexate monotherapy and subsequent response to tumor necrosis factor inhibitors in pediatric non-infectious uveitis (abstract). Arthritis Rheumatol. 2020:72 (suppl 4). Disclosure of Interests Sheila Angeles-Han: None declared, Amy Cassedy: None declared, Theresa Hennard: None declared, Mekibib Altaye: None declared, Hermine Brunner Consultant of: Dr. Brunner’s affiliation Cincinnati Children’s Hospital Medical Center has received consulting fees or other remuneration from AstraZeneca, Boehringer Ingelheim, GSK, Roche, Novartis, Pfizer Inc, Takeda, and UBC for the work of Dr. Brunner. Dr. Brunner is a DSMB member for Janssen Pharmaceutical’s trial of ustekinumab pediatric Crohn and Ulcerative colitis., Grant/research support from: Dr. Brunner’s affiliation Cincinnati Children’s Hospital Medical Center has received research grants from BMS, Janssen, Novartis, Pfizer Inc, Roche, and UBC., Eniolami Dosunmu: None declared, Alexei Grom: None declared, Michael Henrickson: None declared, Jennifer Huggins: None declared, Sarah Lopper: None declared, Daniel J Lovell Consultant of: AstraZeneca, Boehringer Ingelheim, GSK, Roche, Novartis, Pfizer Inc, Takeda, and UBC, Grant/research support from: BMS, Janssen, Novartis, Pfizer Inc, Roche, and UBC, Robert Sisk Consultant of: AGTC, Gyroscope, and Leica, Tracy Ting: None declared, Adam Kaufman Consultant of: Consultant for Alcon, Bausch &amp; Lomb, and 1800contacts, not related or relevant to study content., Virginia Utz: None declared